Marek's disease (MD) is a lymphoproliferative disease, caused by a highly contagious oncogenic herpesvirus, Marek's disease virus. Infection of susceptible chickens with MDV of MD-derived transformed tumor cells (JMV) causes depressed T cell immune responses, as measured in vivo and in vitro. Suppression of T cell immunity may be central to MD pathogenesis. The cellular mechanisms of immunosuppression are being studied. In mixed culture assays, both suppressive and enhancing effects of spleen and thymus cells from MD-infected chickens have been shown. The cells and kinds of interactions which effect these altered responses will be determined. Cell separation procedures, such as Ficoll density gradient fractionation, are facilitating these studies. The suppressive or enhancing effects of specific enriched fractions of cells will be tested. Subpopulations of cells separated in the gradient by density, are being characterized by cell surface antigens and by immune function. Cultures of lymphocytes, macrophages and tumors from MDV- and JMV-infected chickens will be tested for production of suppressive factors (SF). If found in culture fluids, SF will be studied for its effect on the T cell and B cell-mediated immune reaction, both in vivo and in vitro. The nature of immunosuppressive effects exerted by MD cells or factors in the various assay systems, will be assessed in terms of the severity of disease in the MD-infected donor. Studies will be undertaken to determine a possible autoimmune component in MD. The proliferation will be measured in mixed cultures with either mitogen-induced, or MDV-associated lymphoblasts. Autoreactivity of infected chicken thymus and spleen cells will be studied, by plaque assay.